In searching for the drainage route of the interstitial fluid (ISF) in the deep brain, we discovered a regionalized ISF drainage system as well as a new function of myelin in regulating the drainage. The traced ISF from the caudate nucleus drained to the ipsilateral cortex along myelin fiber tracts, while in the opposite direction, its movement to the adjacent thalamus was completely impeded by a barrier structure, which was identified as the converged, compact myelin fascicle. The regulating and the barrier effects of myelin were unchanged in AQP4-knockout rats but were impaired as the integrity of boundary structure of drainage system was destroyed in a demyelinated rat model. We thus proposed that the brain homeostasis was maintained within each ISF drainage division locally, rather than across the brain as a whole. A new brain division system and a new pathogenic mechanism of demyelination are therefore proposed.

It has been reported that aquaporin-4 (AQP4) deficiency impairs transportation between the cerebrospinal fluid and interstitial fluid (ISF) as well as the clearance of interstitial solutes in the superficial brain. However, the effect of AQP4 on ISF flow in the deep brain remains unclear. This study compared the brain ISF flow in the caudate nucleus and thalamus of normal rats (NO) and AQP4 knockout rats (KO) using tracer-based magnetic resonance imaging. The rate of brain ISF flow slowed to different degrees in the two regions of KO rats’ brains. Compared with NO rats, the half-life of ISF in the thalamus of KO rats was significantly prolonged, with a corresponding decrease in the clearance coefficient. The tortuosity of the brain extracellular space (ECS) was unchanged in the thalamus of KO rats. In the caudate nucleus of KO rats, the volume fraction of the ECS and the diffusion coefficient were increased, with significantly decreased tortuosity; no significant changes in brain ISF flow were demonstrated. Combined with a change in the expression of glial fibrillary acidic protein and AQP4 in two brain regions, we found that the effect of AQP4 knockout on ISF flow and ECS structure in these two regions differed. This difference may be related to the distribution of astrocytes and the extent of AQP4 decline. This study provides evidence for the involvement of AQP4 in ISF transportation in the deep brain and provides a basis for the establishment of a pharmacokinetic model of the brain’s interstitial pathway.

Background: Degenerative disorders of the lumbar spine decrease the mobility and quality of life of elderly patients. Lumbar fusion surgery is the primary method of treating degenerative lumbar spine disorders; however, the surgical stress response associated with major surgery has been linked to pathophysiological changes in the elderly, resulting in undesirable postoperative morbidity, complications, pain, fatigue, and extended convalescence. In the present study, we aimed to determine whether enhanced recovery after surgery significantly improved satisfaction and outcomes in elderly patients (> 65 years old) with short-level lumbar fusion. Methods: The study enrolled lumbar disc herniation or lumbar spinal stenosis patients if they were over the age of 65 years old underwent lumbar fusion at one or two levels. Data including demographic, comorbidity, and surgical information were collected from electronic medical records. Enhanced recovery after surgery interventions was categorized as preoperative, intraoperative, and postoperative. We also evaluated primary outcome, surgical complication, length of stay, postoperative pain scores, and 30-day readmission rates.

The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (DECS) and volume fraction (α) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene (APQ4) knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed DECS and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the DECS were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and DECS mapping may be used to track the neuronal activity in the deep brain.

Fat embolism syndrome (FES) is a common complication following long bone fracture; fat droplets are released into the blood circulation and form embolisms, mainly in lung and brain. However, the potential mechanisms involved remain to be clarified. In this study, the mechanism of brain injury following FES and the protective effects of urinary trypsin inhibitor (UTI)—a serine protease inhibitor—were investigated. Sixty male Sprague-Dawley rats were divided randomly into sham, FES and FES+UTI treatment groups. The FES model was established using tail vein injection of glycerol trioleate, and UTI was administered by intraperitoneal injection immediately following FES. Brain/lung water content evaluation, Evans blue content and magnetic resonance imaging examination were used to assess the effects of UTI. Furthermore, immunohistochemistry and western blot were also applied to explore the protective mechanism of UTI following FES. The results of oil red O staining indicated that the FES model was successfully established. UTI could significantly attenuate blood-brain-barrier (BBB) disruption, as seen through brain edema evaluation and Evans blue content examination. Immunofluorescence staining results indicated that the TLR4-JNK pathway was involved in brain injury after FES; this effect could be quenched by UTI treatment. Furthermore, UTI could decrease the levels of downstream target proteins of the TLR4-JNK pathway, phosphorylated-NF- κB (p65) and p53 in brain. Our results showed that UTI could alleviate BBB injury after FES through blocking activity of the TLR4-JNK pathway.